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My work in Prof. Zewail's group involves both analytical and computational approaches to protein folding and dynamics. Molecular dynamics simulations are being used to calculate individual protein folding trajectories and kinetics. With increasing computational power, these trajectories can span longer times, and more can be averaged together to understand what is going on in an ensemble sense. Advanced walking and Monte Carlo techniques are being developed to get ever more detailed pictures of energy landscapes, elucidating the inherent nature and recurring motifs of protein folding in general. We are narrowing in on nature's way of folding proteins on such short timescales. In addition to understanding the general question, protein folding and function simulations and energy landscapes can be used to analyze specific dynamics of interest like protein ion channels, pumps, and protein-DNA interactions. Computationally, this research has been made possible with the new supercomputer in Prof. Zewail's lab.
In addition to computational work, I am also interested in applying techniques and insights from theoretical physics to make predictions about macromolecular behavior. For example, we developed a model for predicting the existence and identity of kinetic intermediates during the unfolding of DNA hairpins using only equilibrium enthalpies and energies of base-pairing and polymer loop formation. In addition, we recently developed a model of hydrogen bond formation in proteins based on Brownian rotational motion of the protein subunits. The analytic predictions of both models were confirmed by MD simulations and experimental results. It is my hope that analytical insight, computational specificity, and experimental confirmation will continue to guide my research.
1) Robert M. Dirks, Milo Lin, Erik Winfree, and Niles A. Pierce. Paradigms for computational nucleic acid design. Nucleic Acids Research, 32(4):1392--1403, 2004. http://nar.oxfordjournals.org/cgi/content/full/32/4/1392
2) Milo Lin, David Prendergast, Giulia Galli. An ab initio study of crystalline and molecular biotin.
American Physical Society, APS March Meeting, March 21-25, 2005, abstract #P34.008
3) Milo M. Lin, Dmitry Shorokhov, Ahmed Zewail. Helix-to-Coil Transitions in Proteins: Helicity Resonance in Ultrafast Electron Diffraction, Chemical Physics Letters, 420:1-7, 2007
4) M. Lin, L. Meinhold, D. Shorokhov, A.H. Zewail. Unfolding and melting of DNA (RNA) hairpins: the concept of structure-specific 2D dynamic landscapes, Phys. Chem. Chem. Phys., 10: 4227, 2008
5) M. Lin, D. Shorokhov, A. H. Zewail. Conformations and Coherences in Structure Determination by Ultrafast Electron Diffraction, J. Phys. Chem., 113: 4075, 2009
6) O. Mohammed, G. Jas, M. Lin, A. H. Zewail. Primary Peptide Folding Dynamics Observed with Ultrafast Temperature Jump. Angie. Chem. Int. Ed. (Frontispiece) 121: 5738, 2009
7) C. Othon , O.H. Kwon , M. M. Lin , A. H. Zewail, Solvation in protein (un)folding: Effect of local and bulk dynamics in the melittin tetramer-monomer transition, Proc. Natl. Acad. Sci. 106: 12593, 2009
8)M. M. Lin, D. Shorokhov, A. H. Zewail, Structural Ultrafast Dynamics of Macromolecules: Diffraction of Free DNA and Effect of Hydration, Phys. Chem. Chem. Phys. 11: 10619, 2009.
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